New cohorts of non-injection drug users (non-IDUs) are at substantial risk of transitioning to injection and of becoming infected with HIV, HBV, and HCV. Moreover, several studies have reported unexpectedly high rates of infection with HCV among individuals reporting no history of drug injection. Other possible routes of transmission of HCV among non-IDUs, such as sexual transmission or the shared use of non-injection drug equipment are still unclear. Puerto Rican drug users have consistently been found to have greater overall HIV risk than drug users of other ethnic/racial backgrounds. Moreover, there is evidence suggesting that Puerto Rican non-IDUs are more likely to make the transition to drug injection and, once injecting, to become infected with HIV and HCV than their counterparts of other ethnic/racial groups. Therefore, the need to increase our understanding of the factors that can account for greater risk among Puerto Rican non-IDUs and new injectors is critical. We propose a prospective cohort study of 720 non-IDUs in Puerto Rico designed to examine transitions to injection, the sexual risk behaviors of non-IDUs, and the risk factors of infection of non-IDUs who transition to injection and those who do not. The sample will be recruited from street settings and will consist of heroin sniffers and crack smokers 18 to 25 years old who have never injected drugs. Participants will be followed-up during a period of two years and re-assessed four times at six-month intervals. Ethnographic/qualitative and quantitative methods and procedures will be utilized. The proposed study is grounded conceptually in several theories and research approaches from which three domains of variables have been derived: 1) Social relationships and social contexts, 2) personality traits, attitudes and beliefs, and 3) drug behaviors and disorders. The data will be analyzed with bivariate analyses and multivariate modeling, including multiple logistic regression, Cox proportional hazards regression, and generalized estimation equations.